The neuroprotective effect of short-chain fatty acids against hypoxia-reperfusion injury

IF 2.6 3区医学 Q3 NEUROSCIENCES

Molecular and Cellular Neuroscience Pub Date : 2024-09-28 DOI:10.1016/j.mcn.2024.103972

Anjit K. Harijan , Retnamony Kalaiarasan , Amit Kumar Ghosh , Ruchi P. Jain , Amal Kanti Bera

{"title":"The neuroprotective effect of short-chain fatty acids against hypoxia-reperfusion injury","authors":"Anjit K. Harijan , Retnamony Kalaiarasan , Amit Kumar Ghosh , Ruchi P. Jain , Amal Kanti Bera","doi":"10.1016/j.mcn.2024.103972","DOIUrl":null,"url":null,"abstract":"<div><div>Gut microbe-derived short-chain fatty acids (SCFAs) are known to have a profound impact on various brain functions, including cognition, mood, and overall neurological health. However, their role, if any, in protecting against hypoxic injury and ischemic stroke has not been extensively studied. In this study, we investigated the effects of two major SCFAs abundant in the gut, propionate (P) and butyrate (B), on hypoxia-reperfusion injury using a neuronal cell line and a zebrafish model. Neuro 2a (N2a) cells treated with P and B exhibited reduced levels of mitochondrial and cytosolic reactive oxygen species (ROS), diminished loss of mitochondrial membrane potential, suppressed caspase activation, and lower rates of cell death when exposed to CoCl<sub>2</sub>, a chemical commonly used to simulate hypoxia. Furthermore, adult zebrafish fed SCFA-supplemented feeds showed less susceptibility to hypoxic conditions compared to the control group, as indicated by multiple behavioral measures. Histological analysis of 2,3,5-Triphenyltetrazolium chloride (TTC) stained brain sections revealed less damage in the SCFA-fed group. We also found that Fatty Acid Binding Protein 7 (FABP7), also known as Brain Lipid Binding Protein (BLBP), a neuroprotective fatty acid binding protein, was upregulated in the brains of the SCFA-fed group. Additionally, when FABP7 was overexpressed in N2a cells, it protected the cells from injury caused by CoCl<sub>2</sub> treatment. Overall, our data provide evidence for a neuroprotective role of P and B against hypoxic brain injury and suggest the potential of dietary supplementation with SCFAs to mitigate stroke-induced brain damage.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"131 ","pages":"Article 103972"},"PeriodicalIF":2.6000,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1044743124000575","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Gut microbe-derived short-chain fatty acids (SCFAs) are known to have a profound impact on various brain functions, including cognition, mood, and overall neurological health. However, their role, if any, in protecting against hypoxic injury and ischemic stroke has not been extensively studied. In this study, we investigated the effects of two major SCFAs abundant in the gut, propionate (P) and butyrate (B), on hypoxia-reperfusion injury using a neuronal cell line and a zebrafish model. Neuro 2a (N2a) cells treated with P and B exhibited reduced levels of mitochondrial and cytosolic reactive oxygen species (ROS), diminished loss of mitochondrial membrane potential, suppressed caspase activation, and lower rates of cell death when exposed to CoCl₂, a chemical commonly used to simulate hypoxia. Furthermore, adult zebrafish fed SCFA-supplemented feeds showed less susceptibility to hypoxic conditions compared to the control group, as indicated by multiple behavioral measures. Histological analysis of 2,3,5-Triphenyltetrazolium chloride (TTC) stained brain sections revealed less damage in the SCFA-fed group. We also found that Fatty Acid Binding Protein 7 (FABP7), also known as Brain Lipid Binding Protein (BLBP), a neuroprotective fatty acid binding protein, was upregulated in the brains of the SCFA-fed group. Additionally, when FABP7 was overexpressed in N2a cells, it protected the cells from injury caused by CoCl₂ treatment. Overall, our data provide evidence for a neuroprotective role of P and B against hypoxic brain injury and suggest the potential of dietary supplementation with SCFAs to mitigate stroke-induced brain damage.

查看原文本刊更多论文

短链脂肪酸对缺氧再灌注损伤的神经保护作用

众所周知，肠道微生物衍生的短链脂肪酸（SCFAs）对包括认知、情绪和整体神经系统健康在内的各种大脑功能有着深远的影响。然而，它们在保护大脑免受缺氧损伤和缺血性中风方面的作用尚未得到广泛研究。在这项研究中，我们利用神经细胞系和斑马鱼模型研究了肠道中富含的两种主要 SCFAs--丙酸盐（P）和丁酸盐（B）--对缺氧再灌注损伤的影响。当神经 2a（N2a）细胞暴露于常用于模拟缺氧的化学物质 CoCl2 时，经 P 和 B 处理的细胞表现出线粒体和细胞膜活性氧（ROS）水平降低、线粒体膜电位丧失减少、caspase 激活被抑制以及细胞死亡率降低。此外，与对照组相比，喂食添加了 SCFA 的成年斑马鱼在缺氧条件下表现出更低的易感性，这体现在多种行为测量上。2,3,5-三苯基氯化四氮唑（TTC）染色脑切片的组织学分析表明，喂食 SCFA 的斑马鱼损伤较小。我们还发现，脂肪酸结合蛋白 7 (FABP7)，又称脑脂结合蛋白 (BLBP)，是一种具有神经保护作用的脂肪酸结合蛋白，在 SCFA 饲喂组的大脑中上调。此外，当 FABP7 在 N2a 细胞中过表达时，它能保护细胞免受 CoCl2 处理造成的损伤。总之，我们的数据清楚地证明了 P 和 B 对缺氧性脑损伤的神经保护作用，并表明膳食中补充 SCFAs 有可能减轻中风引起的脑损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular and Cellular Neuroscience 医学-神经科学

CiteScore

5.60

自引率

0.00%

发文量

审稿时长

37 days

期刊介绍： Molecular and Cellular Neuroscience publishes original research of high significance covering all aspects of neurosciences indicated by the broadest interpretation of the journal''s title. In particular, the journal focuses on synaptic maintenance, de- and re-organization, neuron-glia communication, and de-/regenerative neurobiology. In addition, studies using animal models of disease with translational prospects and experimental approaches with backward validation of disease signatures from human patients are welcome.